April is Parkinson’s disease Awareness Month. This year the date is particularly significant because 2017 is the 200th anniversary of the publication of British apothecary James Parkinson’s “An Essay on the Shaking Palsy”, which is now recognized as a seminal work in describing the disease.

To mark the occasion we talked with Dr. Birgitt Schuele, Director Gene Discovery and Stem Cell Modeling at the Parkinson’s Institute and Clinical Center in Sunnyvale, California. Dr. Schuele recently received funding from CIRM for a project using new gene-editing technology to try and halt the progression of Parkinson’s.

What got you interested in Parkinson’s research?

People often assume I have a family history of Parkinson’s, since many researchers enter the field for that reason, but I don’t. I’ve always been fascinated by neuroscience and how the brain works. During my neurology residency, I worked with a mentor who specialized in the neurogenetics of Parkinson’s, and that sparked my interest.

I’ve now spent 15 years in this field and have gotten to know many people with Parkinson’s—they’ve become my friends. That makes the work personal. I’m driven to find answers, and ultimately a cure.

I see patients every few months and watch their disease progress, especially those with early or young‑onset Parkinson’s. It’s devastating. It affects their lives, their families, their relationships, and even how they talk to their children about genetic risk. Because Parkinson’s keeps worsening, I see firsthand how deeply it impacts people over time. It’s very hard.

Talk about the project CIRM is funding

This project is exciting because it focuses on stopping disease progression—preventing neurons in affected brain regions from dying. One protein, alpha‑synuclein, identified in 1997, is central to this effort. Families with too much alpha‑synuclein develop aggressive, early‑onset Parkinson’s. I’ve followed one such family with four copies of the gene instead of the usual two; their symptoms began in their mid‑30s. Last year, I attended the funeral of a family member who died at 50.

We know excess alpha‑synuclein kills brain cells. If we can lower its levels, we may be able to protect vulnerable neurons. We’re using CRISPR gene‑editing technology to do this. Previous approaches tried to clear the protein after it was made—using methods like immunotherapy. Instead, we’re going upstream, dialing down the gene’s expression, like dimming a light.

The challenge is balance. Too much protein is harmful, but too little also causes problems. The “right” level may vary from person to person.

We’re starting with the most extreme cases—people who produce twice the normal amount. Once we understand how to adjust those levels, we can move on to people with more subtle elevations. It’s a careful, step‑by‑step process, starting with the most severe cases and moving toward the more common ones.

One family’s story

I followed a family that carries four copies of this alpha-synuclein gene (two copies is the normal figure) and the age of onset in this family was in their mid 30’s. Last year I went to a funeral for one of these family members who died from Parkinson’s at age 50.

We know that this protein is bad for you, if you have too much it kills brains cells. So we have an idea that if you lower levels of this protein it might be an approach to stop or shield those cells from cell death.

We are using CRISPR gene editing technology to approach this. In the Parkinson’s field this idea of down-regulation of alpha-synuclein protein isn’t new, but previous approaches worked at the protein level, trying to get rid of it by using, for example, immunotherapy. But instead of attacking the protein after it has been produced we are starting at the genomic level. We want to use CRISPR as a way to down-regulate the expression of the protein, in the same way we use a light dimmer to lower the level of light in a room.

A balance

But this is a balancing act. Too much of the protein is bad, but so is too little. We know if you get rid of the protein altogether you get negative effects, you cause complications. So we want to find the right level and that’s complex because the right level might vary from person to person.

We are starting with the most extreme levels, with people who have twice as much of this protein as is normal. Once we understand that better, then we can look at people who have levels that are still higher than normal but not at the upper levels we see in early-onset Parkinson’s. They have more subtle changes in their production or expression of this protein. It’s a little bit of a juggling act and it might be different for different patients. We start with the most severe ones and work our way to the most common ones.

Patients often ask why progress takes so long.

The truth is, Parkinson’s has been frustrating for researchers too. About 100 years ago, Dr. Lewy described the protein deposits that define the disease. Around 20 years ago, scientists discovered mutations in the alpha‑synuclein gene, and today we know roughly 30 genes linked to Parkinson’s. But for decades, the science was mostly descriptive—it told us what was happening, not why.

For a long time, researchers focused on dopamine loss. Dopamine was identified in 1957, and the success of L‑Dopa in the 1960s reinforced the idea that Parkinson’s was primarily a dopamine‑deficiency disorder.

Progress

Over the last 15 years, we’ve looked more closely and realized the disease is far more complex. Parkinson’s also involves loss of smell, insomnia, depression, and other non‑motor symptoms. In the past decade, evidence has shown it’s a multi‑system disease marked by neuronal death and protein deposits called Lewy bodies. These alpha‑synuclein–filled deposits appear not only in the brain but also in the gut and heart—organs long overlooked because no one connected symptoms like constipation or depression to the disease. Parkinson’s is much more than a single brain‑region problem.

Another barrier to progress is the lack of good disease models that reliably predict clinical outcomes. This is a major reason many neurodegenerative clinical trials have failed. Human induced pluripotent stem cells (iPSCs) are helping change that. iPSC‑derived neurons from people with Parkinson’s now allow researchers to model the disease more accurately and study its mechanisms in the lab. Advances in differentiation techniques mean these neurons behave much more like dopamine‑producing neurons in the brain, marking an important step forward.

Will this lead to a clinical trial?

That’s the goal.

We’re collaborating with Dr. Deniz Kirik at the University of Lund in Sweden, an expert in human‑compatible viral vectors. This joint project will take what we learn from human iPSC cultures and test it in animal models using his gene‑vector technology to see if the same effects appear in vivo.

We’re using a specialized Parkinson’s mouse model developed at UC San Francisco that carries the full human genomic structure of the alpha‑synuclein gene. If the results hold, we hope to move into preclinical testing and then clinical trials within a few years.

What are your hopes for the future?

I hope to help stop Parkinson’s progression. If we can develop a drug that clears accumulated protein in the brain, we may prevent cell death. For someone with early‑stage PD—mild tremor, minor walking issues—halting progression and using low‑dose dopamine therapy to manage symptoms would be close to a cure.

Another priority is developing better biomarkers to identify people at risk before symptoms appear. With early detection and the right tools in place, we could start treatment sooner and prevent the disease from taking hold.

For people who have lived with the disease for a decade and have significant symptoms, regenerative approaches using embryonic or iPSC‑based therapies will take longer to show results. Still, they remain important long‑term goals, and many groups are advancing this work.

Why is Parkinson’s Awareness Month important?

Because despite broad awareness of the disease, misconceptions persist. Parkinson’s is often confused with Alzheimer’s, dementia, or primarily cognitive disorders. Many people don’t realize it affects far more than gait and movement—it involves multiple systems throughout the body.

Related Posts

Whatever happened to stem cells for Parkinson’s?

Parkinson’s disease modeled for the first time in a lab dish

CIRM 2.0: A New Year, a New Start, a New Way to Advance Research

Former CIRM board member writes a personal story on his battle with chronic pain